Calorimetry is used to measure enthalpic changes, including enthalpic changes arising from reactions, phase changes, changes in molecular conformation, temperature variations, and other variations of interest that may occur for a particular specimen. By measuring enthalpic changes over a series of conditions, other thermodynamic variables may be deduced. Calorimetry measurements are commonly used in biophysical and biochemical studies to determine energy changes as indications of biochemical reactions in a specimen. There is a great interest in developing ultra-miniature microcalorimeter devices that require very small volumes of sampled media, e.g. small drops, for accurate detection and measuring of biochemical reactions on, or in proximity to, the microcalorimeter and which can be applied in a manner to quickly measure large numbers of reactions.
A known calorimeter device includes drop merging electrodes and thermometers residing on a substrate. A protein drop and a ligand drop can be deposited at different locations on a drop merging device comprising electrodes. A voltage difference is applied between two adjacent electrodes and electrostatic forces cause the drops to move toward one another until they merge. The thermometers detect the temperature rise resulting from any reaction between the protein drop and the ligand drop as they merge. The temperature rise due to the reaction is typically very small and any loss of heat, for example via heat dissipation, can affect the results of the tests.
Evaporation from the samples can lead to heat effects that are significant compared to the enthalpic changes of interest when the samples, e.g. drops, are small. Small drops have a relatively large surface area to volume ratio, so the evaporative flux from the surface area comprises an enthalpic flux that can be large. When the heat flux from evaporation becomes too large compared to the enthalpic change of interest in a measurement, the evaporation becomes a problem. It is valuable to have a device for minimizing evaporation from samples in ultra-miniature calorimeter devices, thereby minimizing this problem, while maintaining the advantage from using small samples, including samples that comprise small drops.
Samples with small dimensions, including samples comprising small drops, provide a way to perform measurements with a minimum of sample volume, which can be important when the measurements use materials that are expensive, precious, or difficult to attain. In drug discovery or life sciences research, samples often are precious, either because they are difficult to make or are derived from a limited resource. Samples are sometimes not even fully characterized, rendering it unfeasible to make more of the material “on demand”. For example, the sample could be a naturally occurring extract that is difficult to acquire, or it could be a material available only in a limited quantity in a “library” of compounds derived by combinatorial chemistry methods. Samples with small dimensions, including samples comprising small drops, can also be important when performing measurements on an array. Industry standards for dimensions of arrays specify certain dimensions for each site, and it is desirable to stay within the standards. For example, industry standards for a 96-site microarray for drug discovery applications and automated laboratory instrumentation specify a 9 mm pitch, and the pitch for 384-site and 1536-site microarrays are 4.5 mm and 2.25 mm, respectively. If multiple drops are to be located on a site in such arrays, their size must be correspondingly small. For example, for a known calorimeter device, the drops must have a diameter of about 1 mm or less to fit on the sensing regions of the device.
There is also interest in developing devices other than calorimeters wherein controlling thermal or volumetric changes caused by evaporation is important. Typically the samples in such devices have small dimensions, including samples comprising small drops or comprising liquid patterns in which at least one dimension is small enough for evaporative effects to be important. As examples, miniature devices in which thermal effects are used to actuate or move species therein, or in which precise assays require precise control of sample volume, can be adversely affected by evaporation. Minimizing or preventing such adverse effects is important in improving such devices.